Energy-releasing carbon nanotube transponder and method of using same

ABSTRACT

An energy-releasing carbon nanotube transponder comprising a nanocapacitor connected to at least one carbon nanotube and method of using same are described. An adjustable amount of electric energy is stored within the nanocapacitor so that the energy-releasing carbon nanotube transponder delivers either a biologically destructive or a biologically non-destructive electrical charge to target cells in response to biological, chemical or electrical stimuli. 
     An optional biocompatible coating onto the outer surface of the carbon nanotube transponder improves cellular targeting, cellular binding or body tolerance towards the carbon nanotube transponder. Optionally, a molecular label attached to at least one carbon nanotube allows for in vivo tracking of the carbon nanotube transponder. 
     The targeted release of electric energy from the carbon nanotube transponder can, for example, destroy cancer cells in cancer patients, or control the flux of electric wave within a cellular tissue to treat cardiac and/or epileptic patients.

This application is a continuation-in-part of International ApplicationNo. PCT/US2010/048956 filed Sep. 15, 2010, which claims the prioritybenefit under 35 U.S.C. section 119 of U.S. Provisional PatentApplication 61/242,691 filed Sep. 15, 2009.

FIELD OF THE INVENTION

This invention relates generally to nanotechnology, and moreparticularly to a new device, electrically charged and termed anEnergy-Releasing Carbon Nanotube Transponder, and to methods of usingthe charged Energy-Releasing Carbon Nanotube Transponder to treat humanand non-human afflictions by delivering at least one biologicallydestructive electric charge or at least one biologically non-destructiveelectric charge directly within a tissue to be treated.

BACKGROUND OF THE INVENTION

The present invention relates to nanoscale electromechanical devices andtheir use in medical therapy. More particularly, the present inventionrelates to an energy-releasing carbon nanotube transponder that can befabricated from a plurality of carbon nanotubes optionally attached toat least one biomolecule ligand and connected to a nanocapacitor. Suchan energy-releasing carbon nanotube transponder can be placed incellular tissue to treat multiple afflictions.

The term “patient” is usually understood as any person who receivesmedical attention, care, or treatment. However, many afflictions foundin human patients can also be found in s for example cancer. Thepatients of veterinarians are animals. Therefore it should be understoodthat the invention described in this application can be used to treathumans and animals. Moreover, in this application the term “animal”includes any non-human multicellular, eukaryotic organisms such as forexample fish, birds, insects, reptiles, and non-human mammals.

The term “tissue” usually describes an ensemble of cells, notnecessarily identical, that together carry out a specific function. Forexample, organs are formed by the functional grouping together ofmultiple tissues. However, this invention encompasses the field ofnanotechnology, therefore the invention described in this application isso small that it can be used to treat a single cellular entity, forexample a single neuron or a single cancer cell. It should beunderstood, that when the term “tissue” is used in this application, itis meant one or more cells as appropriate for treatment. Moreover, inthis application, the term “cell” includes any “cellular entity” and itshould not be limited to human and animal cells, for example, the term“cell” in this application encompasses bacterial or even viral entities.For example, cancers are sometimes of viral or bacterial origins,therefore the treatment of cancer, as described in this application, canalso include the destruction of the bacterial and/or the viral entitiesthat trigger or promote cancer.

In this application, the term “treatment” should not be limited to asynonym for therapy used to remedy a health problem, but should also bebroadened to mean a process of modifying or altering one or more cells.

Cancer is presently one of the most difficult fatal conditions to treat.President Nixon declared “war” on cancer back in 1971, and research forcancer treatments has remained at a high level since then. Cancer iscaused by the growth of malignant cells in a patient. Conventionaltreatments for cancer seek to kill or inhibit the growth of cancercells, but also kill or inhibit the growth of healthy cells as well. Thesearch for a balance between treating cancer and not killing the patientcan often result in unsuccessful cancer treatment. Therefore, there is aneed for cancer treatments that better target malignant cells withoutdamaging healthy cells.

In brain cancer, infiltrative primary high-grade neoplastic cells in thecentral nervous system (CNS) are often resistant to conventionalchemotherapeutic and radiation therapies. Chemotherapy and radiationadministered both inside the CNS and outside the blood brain barrieroften cannot reach densely packed malignant cells even followingrespective debulking. Moreover, conventional chemotherapeutic agents canhave limited efficacy due to factors ranging from systemic toxicity, toimpaired drug transport secondary to decreased vascularization of theneoplasm core and P-glycoprotein-mediated drug efflux. These limitationsof conventional therapies have inspired investigational nanotechnologyapproaches to therapy.

Epilepsy is one of the world's oldest recognized conditions. The WorldHealth Organization (WHO) estimates that about 50 million peopleworldwide suffer from epilepsy. See WHO Fact Sheet No. 999 (January2009). Epilepsy is caused by sudden, usually brief, electricaldischarges in the brain. The symptoms can range from a brief loss ofattention to prolonged and severe convulsions.

Epilepsy can be thought of as being like an electrical circuit that hasbeen disturbed and has become unstable. Many patients manage theirsymptoms with drugs that inhibit the onset of epileptic seizures.However, many individuals are affected by medically intractable epilepsywhere surgical options are minimal or non-existent. To address theseissues novel treatment approaches are being developed: The delivery oftreatment stimulation contingent on detection of the ictal onset (e.g.seizure) at the epileptic source is the next generation of implantabletechnologies directed toward optimizing containment of epileptic braincircuits. Such technologies are crucial in individuals with medicallyintractable epilepsy where surgical options are minimal or non-existent.Results emerging from the Food and Drug Administration (FDA)-sponsoredinvestigational neurostimulation trials are promising. However, nearlyall patients enrolled in these studies continue to experiencebreakthrough seizures. Relatively bulky intracranial electrodes areutilized in these studies while the number of electrodes that can beimplanted is limited by their size. Moreover, the implantation of amultiplicity of bulky electrode may result in brain tissue damage.Epileptic networks can be complex and may extend well beyond implantedbulky intracranial electrodes. To optimize stimulation of brain tissuewithout using bulky electrodes, a multiplicity of nanodevices can beutilized to target specific brain cells while minimizing potential braindamage.

The energy-releasing carbon nanotube transponder described in thisapplication has significant implications outside of epilepsy. Such anenergy-releasing carbon nanotube transponder can also be used toinvestigate the brain's ability to record and replay the neural codeinvolved in learning and memory, as well as targeting, labeling andablating infiltrative high-grade neoplastic, cancer cells. It can alsobe used, for example, to treat heart afflictions such as acutemyocardial ischemia or ventricular arrhythmias.

The normal electrical conduction of the heart allows for electricalpropagation to be transmitted from the Sinus Node through both atria andforward to the atrioventricular node (AV). The AV node is part of anelectrical control system of the heart that co-ordinates heart rate. Itelectrically connects atrial and ventricular chambers. Briefly, a heartbeat is normally initiated at the level of the sinus node i.e. theelectric impulse-generating (pacemaker) tissue located in the rightatrium of the heart, and thus the generator of normal sinus rhythm.Normal sinus rhythm is the rhythm of a healthy normal heart, where thesinus node triggers the cardiac activation. When the heart's sinus nodeis defective, the heart's rhythms become abnormal—either too fast, tooslow, or a combination. Abnormal heart's rhythms might result in adecreased transport of oxygen to the cardiac muscle, causing lack ofoxygen in the heart muscle. This lack of oxygen in the heart muscle iscalled a myocardial ischemia. If the oxygen transport is terminated in acertain area, for example due to ischemia, the heart muscle dies in thatregion. This is called an infarction.

Ventricular arrhythmias is also caused by an abnormal electricalconduction of the heart. Ventricular arrhythmias is defined as abnormalrapid heart rhythms (arrhythmias) that originate in the lower chambersof the heart (the ventricles). Ventricular arrhythmias includeventricular tachycardia and ventricular fibrillation. Both are lifethreatening arrhythmias. In ventricular arrhythmias, ventricularactivation does not originate from the atrioventricular node and/or doesnot proceed in the ventricles in a normal way.

Both the sinus node and AV node stimulate the cardiac muscle. It istherefore essential to control electric conduction in heart patientssuch as, for example, in patients who suffer from acute myocardialischemia or ventricular arrhythmias.

Implantable cardiac pacers and defibrillators are well-establisheddevices that can revert potentially fatal arrhythmias back to a normalsinus rhythm by electrical stimulation of heart tissue. For example, anartificial pacemaker is a medical device which uses electrical impulses,delivered by electrodes contacting the heart muscles, to regulate thebeating of the heart. Implantable artificial pacemakers are nowadayscurrently used in heart patients such as, for example, in patients whosuffer from acute myocardial ischemia or ventricular arrhythmias.However, these artificial pacemakers are often associated with anincreased risk for cardiac complications because an artificial pacemakeris an implanted bio-mechanical device that requires routine inspectionand maintenance.

To optimize stimulation of cardiac tissue, nanodevices can be utilizedto target specific cardiac cells. Nanosensors are emerging that candetect hydrogen ions resulting from cardiac ischemic changes. SeeRamachandran et al, Design and fabrication of nanowire electrodes on aflexible substrate for detection of myocardial ischemia, Proceedings ofSPIE Conferences on Nanosensors, Biosensors, and Info-Tech Sensors andSystems; The International Society for Optical Engineering (2009).However, nanosensor-triggered electrical energy-releasing devices do notcurrently exist that can detect anaerobic metabolism due to a lack ofoxygen to trigger release of electrical energy used to defibrillateheart muscle syncytium and/or pacer cells.

Therefore, the energy-releasing nanodevice, disclosed in thisapplication, that can be designed to target specific cells and/orrelease a tunable level of energy offers a great advantage over thecurrent state-of-the-art implantable devices. Moreover, a plurality ofsuch energy-releasing nanodevices can be delivered at close proximity ofthe target cells rapidly through minimally invasive methods.

Carbon nanotubes (CNT) were discovered in the early 1990s as a productof arc-evaporation synthesis of fullerenes. See Iijima, Helicalmicrotubules of graphitic carbon, Nature 354:56-58 (1991). The name“Carbon nanotubes” is derived from their size, since the diameter of ananotube is on the order of a few nanometers (approximately 1/50,000thof the width of a human hair).

Carbon nanotubes have unique chemical and physical properties includingultra light weight, high mechanical strength, high electricalconductivity, and high thermal conductivity. See Sinha and Yeow, Carbonnanotubes for biomedical applications, IEEE Transactions onNanoBioscience, 4:180-195 (2005). These characteristics make CNT a novelnanomaterial for various biomedical applications. See Ji et al, Carbonnanotubes in cancer diagnosis and therapy. Biochimica et BiophysicaActa—Reviews on Cancer, 1806(1):29-35 (2010). Recently, research hasfocused on investigation of targeted delivery of functionalized carbonnanotubes to specific sites of interest. CNT can behave either as ametal or a semiconductor depending on their chiral vector. SeeDresselhaus et al., Carbon Nanotubes:Synthesis, Properties andApplications, Springer, Berlin (2001). However, many of these propertiescan be addressed once the CNT are conjugated with different molecules.

CNT are also appropriate nanomaterials based on their unique electricalproperties making them a good candidate for overcoming the limitationsof convection enhanced delivery (CED) systems. Although CED systems havepromising advantages due to the increased volume of drug distribution inthe brain, the high pressures required for CED have a high risk ofdamaging the tissue. Moreover, these high pressures may result inbackflows along the catheter causing poor drug distribution. See Sampsonet al., Poor drug distribution as a possible explanation for the resultsof the PRECISE trial, Journal of Neurosurgery. 113(2):301-309 (2010).

One category of nanotube is single-walled nanotubes (SWNT). SWNT canexhibit electric properties such as high electrical conductivity thatare electrically useful. SWNT are one likely candidate for miniaturizingelectronics beyond the micro electromechanical scale currently used inelectronics. SWNT can be integrated into complex assemblies throughchemical functionalization which utilizes chemical covalent bondingbetween SWNT and a molecular conjugate. See Ramanathan et al.,Amino-Functionalized Carbon Nanotubes for Binding to Polymers andBiological Systems. Chemistry of Materials, 17:1290-1295 (2005). Anextensive ultrasonic treatment of SWNT allows for an oxidation processthat leads to the opening of the tube caps and the formation of holes inthe sidewalls introducing oxygen containing groups. This process usesthe concept of the Stone-Wales defect that creates these functionalgroups on 2-3% of the sidewall area of carbon nanotubes. These groupscan be chemically modified to create carbon nanotube composites. SeeBalasubramanian and Burghard, Chemically Functionalized CarbonNanotubes. Small, 1:180-192 (2005). Due to the CNT size and structurethey cannot be easily visualized using conventional optical and confocalmicroscopes. Chemical functionalization with fluorescein labels is oneexample of a technique for visualizing CNT, and linking associatedtherapeutic molecules to CNT. In effect, a type of nanocarrier drugdelivery or diagnostic system can be developed.

In the prior art, investigational nanotechnology approaches are at astage that offers a proof of principle demonstrating amelioration ofcancer treatment by two emerging strategies. Namely, 1) targeted drugdelivery using drugs attached to nanoparticles (See Murad et al,Real-time, image-guided, convection-enhanced delivery of interleukin 13bound to pseudomonas exotoxin, Clin Cancer Res. 12(10):3145-3151 (2006);Liu et al, Drug delivery with carbon nanotubes for in vivo cancertreatment. Cancer Res 15; 68(16):6652-6660 (2008)), and 2) targetedrelease of thermal energy using nanoparticles capable of emittingdestructive thermal energy following absorption of external laser orelectromagnetic wavelength energies. See Park et al, Cooperativenanomaterial system to sensitize, target, and treat tumors. Proc NatlAcad Sci USA 107(3):981-986 (2010); Kam et al, Carbon nanotubes asmultifunctional biological transporters and near-infrared agents forselective cancer cell destruction. Proc Natl Acad Sci USA.102(33):11600-11605 (2005); Ganon et al, Carbon nanotube-enhancedthermal destruction of cancer cells in a noninvasive radiofrequencyfield. Cancer. 110(12):2654-65 (2007).

One significant way to enhance the therapeutic index of anticancer drugsis to specifically deliver these agents directly to tumor cells whilebeing carried by a nanosized carrier. This approach can keep theanticancer drugs away from healthy cells that would otherwise be damagedby the toxic effects of these drugs. See Sapra and Allen,Ligand-targeted Liposomal Anticancer Drugs, Progress in Lipid Research42(5):439-462 (2003). Such target-oriented delivery systems include thedelivery of microspheres, nanoparticles and liposomes. See Okada et al,Gene therapy for brain tumors: cytokine gene therapy using DNA/liposome(series 3), No Shinkei Geka 22:999-1004 (1994); Kakinuma et al,Targeting chemotherapy for malignant brain tumor using thermosensitiveliposome and localized hyperthermia, J Neurosurg 84:180-184 (1996).

Alternatively, instead of delivering anticancer drugs withnanoparticles, other nanoparticles are currently being tested inlaboratory conditions to focus energy absorbed from external lasers toablate tumor cells throughout the body. See Von Maltzahn et al,Computationally guided photothermal tumor therapy using long-circulatinggold nanorod antennas, Cancer Res 69:3892-3900 (2009).

A fundamental element required for the successful deployment ofstrategies aimed at targeting particular cells is the ability toidentify surface molecules expressed by, for example, tumor cells andabsent in surrounding healthy cells. Therefore, neoplasm avid functionalbiomolecules such as monoclonal antibodies and proteins conjugated tonanoparticles is essential to a tumor cell targeting system. See Huwyleret al, By-passing of P-glycoprotein using immunoliposomes. J DrugTarget. 10(1):73-9 (2002).

The expression of the interleukin-13 (IL-13) receptor is one of severaltargets over-expressed in 60-80% of high-grade astrocytoma cells i.e.cancer cells also known as Gliobalstoma multiforme (GBM). See Kioi etal, Convection-enhanced delivery of interleukin-13 receptor-directedcytotoxin for malignant glioma therapy. Technol Cancer Res Treat.5(3):239-50 (2006). Human IL-13 is a cytokine protein secreted byactivated T cells that elicits both pro-inflammatory andanti-inflammatory immune responses. See McKenzie et al, Interleukin 13,a T-cell-derived cytokine that regulates human monocyte and B-cellfunction. Proc Natl Acad Sci USA. 90(8):3735-9 (1993); Minty et al,Interleukin-13 is a new human lymphokine regulating inflammatory andimmune responses. Nature. 362(6417):248-50 (1993). IL-13 has tworeceptor subtypes: IL-13/4R and IL-13R-alpha2. The former receptor ispresent in normal cells with high affinity binding shared with IL-4. Thelatter receptor, IL-13R-alpha2, does not bind IL-4. See Caput et al,Cloning and characterization of a specific interleukin (IL)-13 bindingprotein structurally related to the IL-5 receptor alpha chain. J BiolChem. 271(28):16921-6 (1996). IL-13R-alpha2 is associated withhigh-grade astrocytomas and is not significantly expressed in normaltissue, with the exception of the testes. See Caput et al, 1996;Debinski et al, Molecular expression analysis of restrictive receptorfor interleukin 13, a brain tumor-associated cancer/testis antigen. MolMed. 6(5):440-9 (2000). Pilocytic astrocytomas, the most commonastrocytic tumors in children, also over express the IL-13R-alpha2receptor. See Kawakami et al, Analysis of interleukin-13 receptor alpha2expression in human pediatric brain tumors. Cancer. 101(5):1036-42(2004). In effect, the IL-13R-alpha2 receptor exists as an excellentpotential target for delivering cytotoxic molecules to a variety ofdevastating brain tumors.

A number of attempts to use the IL-13R-alpha2 receptor of GBM as atarget for brain cancer therapy have been reported both in vitro and invivo. Some of the successful modalities attempted include, IL-13-basedcytotoxins (See Nash et al, Molecular targeting of malignant gliomaswith novel multiply-mutated interleukin 13-based cytotoxins. Crit RevOncol Hematol. 39(1-2):87-98 (2001); Husain & Puri, Interleukin-13receptor-directed cytotoxin for malignant glioma therapy: from bench tobedside. J Neurooncol. 65(1):37-48 (2003); Kioi et al, (2006); Murad etal, (2006)), IL-13R-alpha2-targeted viruses (See Zhou et al, Engineeredherpes simplex virus 1 is dependent on IL-13R-alpha2 receptor for cellentry and independent of glycoprotein D receptor interaction. Proc NatlAcad Sci USA. 99(23):15124-9 (2002)), and IL-13R-alpha2 immunotherapy(See Mintz et al, Molecular targeting with recombinant cytotoxins ofinterleukin-13 receptor alpha2-expressing glioma. J Neurooncol.64(1-2):117-23 (2003); Kawakami et al, Intratumor administration ofinterleukin-13 receptor-targeted cytotoxin induces apoptotic cell deathin human malignant glioma tumor xenografts. Mol Cancer Ther.1(12):999-1007 (2002)).

As a nanocarrier, CNT have been utilized as excellent candidates forattaching drug molecules, and imaging markers from radiotracers (SeeSingh et al, Tissue biodistribution and blood clearance rates ofintravenously administered carbon nanotube radiotracers. Proc Natl AcadSci USA. 103(9):3357-62 (2006)) to colorimetric labels (See Lee et al,Carbon nanotube-based labels for highly sensitive colorimetric andaggregation-based visual detection of nucleic acids. Nanotechnol. 18(45)455102.1-455102.9 (2007)). Although metal contaminants used to catalyzethe synthesis of CNT can potentially contribute to toxicity,biocompatibility can be achieved with new CNT purification techniques.See Lu et al, Advances in bioapplications of carbon nanotubes. AdvMaterials. 21:139-152 (2009); Liu et al, Drug delivery with carbonnanotubes for in vivo cancer treatment. Cancer Res. 68(16):6652-60(2008); Schipper et al, A pilot toxicology study of single-walled carbonnanotubes in a small sample of mice. Nat Nanotechnol. 3(4):216-21(2008); Yang et al, Long-term accumulation and low toxicity ofsingle-walled carbon nanotubes in intravenously exposed mice. ToxicolLett. 181(3):182-9 (2008). Moreover, neural cells have demonstrated apreference for growing on CNT scaffolding. See Lee & Parpura, Wiringneurons with carbon nanotubes. Front Neuroengineering. 29; 2:8 (2009).CNT are promising nanoscaffolds for transporting biological ligands fordiagnostic and therapeutic purposes including crossing cell membranes,particularly for proteins less than 80 kDa. See Panarotto et al,Translocation of bioactive peptides across cell membranes by carbonnanotubes. Chem Commun (Camb). (1):16-7 (2004). Once a protein ligand isbound to CNT, it has been shown to remain bound under ambientconditions. See Gruner, Carbon nanotube transistors for biosensingapplications. Anal Bioanal Chem. 384(2):322-35 (2006).

The conducting ability of CNT makes these carbon-rich nanostructuresimpressive electromagnetic energy transducers. See Khatpal et al,Polyfunctionalized single-walled carbon nanotubes as a versatileplatform for cancer detection and targeted dual therapy. Intel STSAbstract (2009). The carbon atoms comprising the building blocks of CNTdemonstrate a defined periodicity throughout the nanostructure. Thisproperty gives CNT the ability to efficiently transfer electrons.Therapeutically, these electronic properties of CNT along with thesignificant surface area of CNT can be harnessed. For example, the CNTbackbone of such novel nanostructures potentially can be transportedthrough a medium using an electromagnetic field. In addition, thesemiconducting properties of CNT can potentially deliver focused energyto ablate neoplastic cells by converting radiofrequencies into heat. SeeGannon et al, Carbon nanotube-enhanced thermal destruction of cancercells in a noninvasive radiofrequency field. Cancer. 110(12):2654-65(2007).

The technologies described in the prior-art differ from the inventiondisclosed in this application. The invention disclosed in this inventionrelies on nanotechnology that can be applied to treat, for example,brain cancers, cardiovascular diseases and brain afflictions such asepilepsy.

This application describes a novel nanoparticle. It also describes themethod of using it to therapeutically treat cells inside patient tissueby delivering electrical energy to those cells. The nanoparticlepossesses a molecular detection system and a nanocapacitor. Thenanoparticle discharges electrical energy to cells even when those cellsare found deeply embedded in a patient's tissue. Self-containednanosensors that are integrated with nanocapacitor charging capabilityto stimulate the microenvironment in response to local changes do notexist in the prior-art. This disclosure describes a novel nanoparticleof up to 500 nanometers in diameter since it has been shown that ananoparticle of up to 500 nanometers in diameter is capable of crossingthe blood-brain barrier in certain disease states such as epilepsy andbrain cancers.

The present disclosure also relates to nanoparticles that can be made todischarge different amounts of energy. These novel nanoparticles can beconcurrently introduced into one or more epileptic circuits in the brainto detect changes during seizure activity (e.g., nanomolar increases inthe transmitter glutamate). A detection threshold can be used todischarge the nanocapacitor of these novel nanoparticles to deliverdirect stimulation therapy to potentially stabilize the epilepticcircuit. By releasing specific amounts of energy, the nanoparticles ofthe current disclosure can also damage or destroy disease-inducingcells, stabilize the activity of neurons or other cells such as cardiaccells. The present disclosure also relates to nanoparticles that containa nanocapacitor that can be recharged in energy once the nanoparticleshave been discharged.

BENEFITS OF THE INVENTION

It is a first benefit of the present invention to provide anenergy-releasing carbon nanotube transponder to deliver at least oneelectric charge to a tissue.

It is a further benefit of the instant invention to provide a method forthe energy-releasing carbon nanotube transponder to release abiologically non-destructive electric charge.

It is another benefit of the invention to provide a method for theenergy-releasing carbon nanotube transponder to release a biologicallydestructive electric charge.

It is an additional benefit of the invention to provide a method totreat cancer, for example brain cancer.

It is still an additional benefit of the invention to provide a methodto stabilize brain electrical circuits, for example in patients whosuffer from seizures or epilepsy.

Another additional benefit of the invention is to provide a method totreat cardiac disease, for example in patients who suffer from acutemyocardial ischemia or ventricular arrhythmias.

These and other benefits of the invention will more readily becomeapparent from the description and examples which follow.

BRIEF DESCRIPTION OF THE DRAWINGS

The FIGURE is a diagram of an energy-releasing carbon nanotubetransponder 10.

Optionally, a biomolecule ligand 14 is covalently attached to an end ofat least one carbon nanotube 12 to form a nanosensor 16 i.e. sensingelement of the present disclosure. A nanocapacitor 18 is connected tothe opposite end of at least one of the carbon nanotube 12. Theassociation of the optional biomolecule ligand 14, at least one carbonnanotube 12 and the nanocapacitor 18 forms the energy-releasing carbonnanotube transponder 10. Optionally, the outer surface of theenergy-releasing carbon nanotube transponder 10 can be coated with atleast one biocompatible molecule to form a biocompatible coating 20, forexample to improve cellular binding or body tolerance towards theenergy-releasing carbon nanotube transponder 10. Optionally, at leastone molecular label 22 such as a radiolabel is covalently attached to anend of at least one carbon nanotube 12 to allow for in vivo tracking ofthe energy-releasing carbon nanotube transponder 10. Optionally, acoiled nanowire located inside (24 a) the nanocapacitor 18, oralternatively by design, outside (24 b) the nanocapacitor 18, allows forthe energy-releasing carbon nanotube transponder 10 to be recharged inenergy once it has been discharged.

SUMMARY OF THE INVENTION

According to an embodiment of the present disclosure, anenergy-releasing carbon nanotube transponder is provided. A transponderis normally defined as an automatic device that transmits apredetermined signal in response to a predefined received signal.However, the term transponder is used in an unconventional way in thisapplication. In the present disclosure, at the cellular level, theenergy-releasing carbon nanotube transponder can transmit an electricaldischarge in response to the binding of a specific biomolecule ligand toits cellular receptor and/or the detection of a specific electricalfield condition and/or the detection of a predetermined concentration ofspecific chemicals in the environment of the energy-releasing carbonnanotube transponder.

The energy-releasing carbon nanotube transponder includes at least onecarbon nanotube connected to a nanocapacitor. Optionally, a nanosensoris formed by at least one biomolecule ligand covalently attached to anend of at least one carbon nanotube. The nanocapacitor is connected tothe opposite end of at least one of the carbon nanotube.

According to an embodiment of the present disclosure, the association ofthe nanocapacitor to the nanosensor forms the energy-releasing carbonnanotube transponder. The energy-releasing carbon nanotube transponderis optionally coated with at least one biocompatible molecule to form abiocompatible coating. The energy-releasing carbon nanotube transponderis optionally labeled with at least one molecular label.

According to an embodiment of the present disclosure, theenergy-releasing carbon nanotube transponder releases a biologicallynon-destructive electric charge to target cells.

According to an embodiment of the present disclosure, theenergy-releasing carbon nanotube transponder releases a biologicallydestructive electric charge to target cells.

According to an embodiment of the present disclosure, a method fordamaging disease-promoting cells is provided. The method includes thestep of positioning the energy-releasing carbon nanotube transponderdisclosed in this application in the biological tissue to be treated.

According to an embodiment of the present disclosure, a method fortreating cancer is provided. The method includes the step of positioningthe energy-releasing carbon nanotube transponder disclosed in thisapplication in the cancer tissue to be treated. The method includes thestep of delivering a biologically destructive charge in the cancertissue in order to treat cancer cells.

According to an embodiment of the present disclosure, a method formodifying the electric field within cellular tissues is provided. Themethod includes the step of positioning the energy-releasing carbonnanotube transponder disclosed in this application in the biologicaltissue to be treated.

According to an embodiment of the present disclosure, a method fortreating epilepsy is provided. The method includes the step ofpositioning the energy-releasing carbon nanotube transponder disclosedin this application in the brain tissue to be treated. The methodincludes the step of delivering a biologically non-destructive charge inthe brain tissue in order to stabilize electrical circuits in the brainsof patients with epilepsy.

According to an embodiment of the present disclosure, a method fortreating cardiac disease is provided. The method includes the step ofpositioning the energy-releasing carbon nanotube transponder disclosedin this application in the tissue that affects cardiac functions. Themethod includes the step of delivering a biologically non-destructivecharge in the heart-related tissue in order to treat cardiac disease(e.g. acute myocardial ischemia and ventricular arrhythmias).

DESCRIPTION OF THE PREFERRED EMBODIMENTS

While the present disclosure may be embodied in many different forms,and may be used to affect various cellular tissues, a number ofillustrative embodiments are described herein with the understandingthat the present disclosure is to be considered as providing examples ofthe principles of the invention and such examples are not intended tolimit the invention to preferred embodiments described or illustrated.

Referring to the FIGURE, the energy-releasing carbon nanotubetransponder 10 integrates at least one carbon nanotube 12 attached to ananocapacitor 18. Optionally, the energy-releasing carbon nanotubetransponder 10 also integrates at least one carbon nanotube 12 attachedto a biomolecule ligand 14 in order to form a nanosensor 16 subassembly.Optionally, the energy-releasing carbon nanotube transponder 10 alsointegrates at least one carbon nanotube 12 attached to a molecular label22. Optionally, a coiled nanowire located inside (24 a) thenanocapacitor 18, or alternatively by design, outside (24 b) thenanocapacitor 18, allows for the energy-releasing carbon nanotubetransponder 10 to be recharged in energy once it has been discharged.

Carbon nanotubes 12 can be synthesized through methods well-known in theart. These methods include: electric arc discharge, laser ablation, andcatalytic chemical vapor deposition (CCVD). See Iijima, Helicalmicrotubules of graphitic carbon, Nature 354:56-58 (1991); Thess et al,Crystalline ropes of metallic carbon nanotube, Science 273: 483-487(1996); Yudasaka et al, Single-walled nanotube formation by laserablation using double-targets of carbon and metal, Chem Phys Lett278:102-106 (1997); Baddour and Briens, Carbon nanotube synthesis: areview, Int. J Chem Reactor Eng 3:R (2005).

An operative embodiment can make use of a plurality of single wallcarbon nanotubes 12 (SWCNT) characterized by electric conductivity andbiocompatibility. SWCNT are like a sheet of carbon atoms rolled into acylinder that is about 3.5 nanometers in diameter (about 1/50,000 thediameter of a human hair), however, the present disclosure alsoencompasses the utilization of other carbon nanotubes. SWCNT possesscharacteristics of a conductive metal. It has been shown that theinterior of the SWCNT cylinder can guide electrons down its length. Thisinnate conductivity can be altered along the nanotube by attaching, forexample, biomolecules such as biomolecule ligands. See Chen et al, Aninvestigation of the mechanisms of electronic sensing of proteinadsorption on carbon nanotube devices. J Am Chem Soc. 126(5):1563-8(2004); Ishikawa et al, Rapid and label-free cell detection bymetalcluster-decorated carbon nanotube biosensors. BiosensorsBiolelectronics 24: 2967-2972 (2007); Chen et al., Functionalizedsingle-walled carbon nanotubes as rationally designed vehicles fortumor-targeted drug delivery, J. Am. Chem. Soc. 130:16778-16785 (2008);Ishikawa et al, Label-free, electrical detection of the SARS virusN-protein with nanowire biosensors utilizing antibody mimics as captureprobes. ACS Nano. 3(5):1219-24 (2009).

One optional way to alter the electrical conductivity of a carbonnanotube 12 is by attaching at least one biomolecule to it. Such abiomolecule can be covalently attached to a carbon nanotube by thesharing of pairs of electrons between atoms. These biomolecules can beligands for receptors i.e. biomolecule ligand 14. The binding of ligandsto receptors occurs by intermolecular forces, such as ionic bonds,hydrogen bonds and Van der Waals forces.

The response of a nanosensor 16 involves three characteristics; 1) theelectrostatic interaction between the net charge of a biomolecule, acarbon nanotube and counter ions in buffer; 2) movement or transport ofthe biomolecule to a receptor or marker and 3) alteration of theconductance of the carbon nanotube 12. For example, a nanosensor 16formed by the attachment of a biomolecule ligand 14 to a carbon nanotube12 can be introduced into one or more epileptic circuits to detectchanges during seizure activity (e.g., femtomolar increases in theneurotransmitter glutamate correlates to an increased conductivity ofthe carbon nanotube 12 of the nanosensor 16. A detection threshold ofthe energy-releasing carbon nanotube transponder 10 can be used todischarge a nanocapacitor 18 to deliver direct stimulation therapy topotentially stabilize the epileptic circuit.

A capacitor functions much like a battery but charges and dischargesmuch more efficiently. A nanocapacitor 18 is a nanostructure largeenough to connect to at least one carbon nanotube 12. The nanocapacitor18 has a capacity for storing an electric charge appropriate to itsapplication. The method of charging the nanocapacitor 18 is according tothe requirements of the particular nanocapacitor 18. An example of asuitable nanocapacitor can be provided by a nanotechnology company suchas SolRayo, Inc, Madison, Wis. Optionally, a coiled nanowire locatedinside (24 a) the nanocapacitor 18, or alternatively by design, outside(24 b) the nanocapacitor 18, allows for the energy-releasing carbonnanotube transponder 10 to be recharged in energy once it has beendischarged.

In the first exemplary embodiment, the nanocapacitor 18 and theenergy-releasing carbon nanotube transponder 10 release biologicallydestructive electric charge densities in the range of between about 21and about 30 microCoulombs/cm² and preferably about 23microCoulombs/cm². In the second exemplary embodiment, the nanocapacitor18 and the energy-releasing carbon nanotube transponder 10 releasebiologically non-destructive electric charge densities in the range ofbetween about 4 and about 20 microCoulombs/cm².

Noncovalent functionalization of carbon nanotube 12 can be performed topreserve the bioactivity of the biomolecule ligand 14. See Panchapakesanet al, Single-wall carbon nanotubes with adsorbed antibodies detect livebreast cancer cells, NanoBiotech 1:353-360 (2005). Detection of a boundligand and biomolecules has been performed by monitoring the electricalcurrent through the carbon nanotube 12 under a 5 mV bias during ligandand biomolecule. Charge transfer has been shown to occur between carbonnanotube 12 bound antibodies and certain cancer cells to which theantibodies can bind. Binding to an antigen-specific antibody can producea several-fold increase in electrical conductance of the carbon nanotube12 compared to binding using nonspecific antibodies. Ibid.

Antibodies or proteins associated with particular afflictions are firstidentified using common biomolecular methodologies. For example, aglutamate detecting protein construct ligand has been identified andused for detection of nanomolar changes of the transmitter glutamate atthe surface of living cells. See Okumoto et al, Detection of glutamaterelease from neurons by genetically encoded surface-displayed FRETnanosensors, PNAS 102:8740-8745 (2005). Another example is carbonnanotube 12 binding to high grade brain glioma cells expressing humaninterleukin-13R-alpha2 (IL-13Ra2) receptors. See Minty et al,Interleukin-13 is a new human lymphokine regulating inflammatory andimmune responses, Nature 362:248-250 (1993); McKenzie et al, Interleukin13, a T-cell-derived cytokine that regulates human monocyte and B-cellfunction, Proc Natl Acad Sci USA 90:3735-3739 (1993). The IL-13R-alpha2receptor is a specific cell membrane biomarker for cancer cells. IL-13is an example of biomolecule ligand for the IL-13R-alpha2 receptor.Ligand binding to a carbon nanotube can be optimized to generate largequantities of nanoparticles suitable for patient treatment. The servicesof a company such as Phosphorex, Inc, Fall River, Mass., can be used forthat purpose and, for example, to optimize the binding of thebiomolecule ligand IL-13 onto carbon nanotubes. The biomolecule ligand14 specific to the receptors/markers are then produced and covalentlylinked to at least one carbon nanotube 12 to form the nanosensor 16element of the present disclosure.

Alternatively, the nanosensor 16 element of the invention can becalibrated in order to allow for the release of electrical energy fromthe nanocapacitor 18 at a pre-determined modification in theconductivity of the carbon nanotube 12. More specifically, the presenceof the energy-releasing carbon nanotube transponder 10 in apre-determined electrical field suffices to trigger the release of thestored electrical energy from the nanocapacitor 18 even in absence ofbinding between a biomolecule ligand 14 and its receptor.

Optionally, a biocompatible coating 20 surrounds the energy-releasingcarbon nanotube transponder 10, for example, to improve bio toleranceand/or adherence of the energy-releasing carbon nanotube transponder 10onto target cells. For example, the nanotransponder presently disclosedcan be coated with an amphilic copolymer, such as PEG molecules, thatcan enhance biocompatibility of the nanodevice. Similar polymers havebeen used in drug delivery. See Allen et al, Nano-engineering blockcopolymer aggregates for drug delivery, Colloids Surf B: Biointerfaces16:3-27 (1999). The charged transponder 10 can be carefully inserted ina cellular tissue with a probe, needle or catheter for example. SeeRossi, Optimizing termination of the ictal onset: On-demand pulsatileintracerebral delivery of RWJ-333369 with responsive neurostimulation,Johnson & Johnson Grant PAR-2007-0001255 (2007). Suitable neural probescan be purchased from companies such as NeuroNexus Technologies, Inc.,Ann Arbor, Mich. NeuroNexus fluidic microelectrode probes can allow fora very precise positioning of nanoparticles in the brain. Neural probescan also be used to measure alterations in local electric fieldsgenerated by neurons. For therapeutic applications, a plurality ofenergy-releasing carbon nanotube transponders 10 can be implanted withina tissue to be treated. The required number of energy-releasing carbonnanotube transponder is typically greater than 1000 but can also besmaller as required by treatment.

Alteration in conductivity can be measured across the carbon nanotube 12using a well-developed cantilever technique to hold the carbon nanotube12 in place. In practice, depending on the targeted cells,Interleukin-13 can be switched out for any biomolecule ligand 14 ofinterest to a bioreceptor on or inside a neural cell for example.

Such alteration in conductivity can be precisely measured using asemiconductor parameter analyzer e.g. HP4516, capable of measuringfemtoAmps (fA) of electrical current with high accuracy. SeePanchapakesan et al, (2005). Accordingly, a method of selecting a ligandfrom possible ligands to bind to one type of target cells can beselected from known target cell receptor types. One nanocapacitor 18 canstore a mean charge density from about 1.2×10⁻⁵ to about 2.4×10⁻⁵Coulombs/cm². This storage capacity allows for a plurality ofenergy-releasing carbon nanotube transponders to deliver an electricalcharge in the range from about 4 to about 30 microCoulombs/cm².

The amount of electric energy to be administered differs according tovarious parameters such as for example, the tissue, the localization ofthe target and the purpose of the treatment. Methods to predict thepropagation of electric fields within tissues have been published. Theycan be utilized to optimize placement of energy-releasingnanotransponders and to determine the optimum amount of electric energythat need to be released. For example, Rossi et al (2010), provide amethod to predict propagation pattern of electrical current in braintissue, including epileptic tissue during neurostimulation therapy. SeeRossi et al, Predicting white matter targets for direct neurostimulationtherapy. Epilepsy Res. 91(2-3):176-186 (2010). This method predicts theoptimum brain location where an electric discharge can be initiated totreat brain afflictions such as for example epilepsy. After electricstimulation of brain tissue, this method allows for the validation ofthe choice of the location where electric stimuli were previouslyinitiated. Rossi et al (2010) allowed for the determination of theoptimum electric charge to be delivered in a human patient who sufferedfrom epileptic seizures. This method allowed for the delivery in a humanpatient of a biologically non-destructive charge of 9.1microCoulombs/cm² to abort seizures without injuring brain cells.

The outer surface of the energy-releasing carbon nanotube transponder 10can be coated with at least one biocompatible molecule 20, for exampleto improve cellular binding or body tolerance towards theenergy-releasing carbon nanotube transponder 10.

Optionally, a molecular label such as a radiolabel 22 is covalentlyattached to at least one carbon nanotube 12 to allow for in vivotracking of the energy-releasing carbon nanotube transponder 10. Suchmolecular label is also useful to insure proper positioning of theenergy-releasing carbon nanotube transponder 10. Carbon nanotubes havebeen utilized for attaching molecular labels such as imaging markersmade of radiotracers (See Singh et al, (2006)) and colorimetric labels(See. Lee et al, (2007)). Examples of radiotracers include technetium(99 mTc) (See Wu et al, Covalently combining carbon nanotubes withanticancer agent: preparation and antitumor activity. ACS Nano.3(9):2740-50 (2009)) or indium-111 (See. Singh et al, (2006)). Dependingon treatment or on the length of time when tracking of the optionalmolecular label 22 is desired it is possible to use for exampleindium-111 that possesses a half-life of 67 hours over for exampleTechnetium that possesses a half-life of only 6 hours. In any case,published protocols can easily be adapted to particular needs. Forexample, Singh et al, (2006) and Wu et al, (2009), provide methods forcoupling indium and technetium, respectively, to a carbon nanotube 12.

Optionally, the biomolecule ligand 14-cellular receptor binding eventcan be detected by a passive Radio Frequency Identification Device(RFID) to trigger a signal to be transmitted to an external receiver.The utilization of a RFID allows for the transmission of dataidentifying changes in the surrounding micro-environment of theenergy-releasing carbon nanotube transponder 10.

In an exemplary embodiment, the nanocapacitor 18 is initially triggeredautomatically by changes in the microenvironment of the energy-releasingcarbon nanotube transponder 10, as known in the art. These changes canbe defined as for example, the binding of the biomolecule ligand 14 to acellular receptor (e.g. the biomolecule ligand IL-13 binding to thecellular receptor IL-13R-alpha2), or a change in ions concentration(e.g. changes in hydrogen ions concentration), or a change in a chemicalconcentration (e.g. changes in glutamate concentration) or changes in anelectric field surrounding the energy-releasing nanoscale transponder 10(e.g. changes due to modification of the electric field of a braintissue or a heart tissue). Such changes in the microenvironment of theenergy-releasing nanoscale transponder 10 can cause an increase inconductance of at least one carbon nanotube 12 of the energy-releasingnanoscale transponder 10 by a factor of at least 2 to 10 (SeePanchapakesan et al, (2005)). Such changes in impedance or conductivityof at least one carbon nanotube 12, function as a nanoswitch thattriggers the discharge of the electrical energy stored in thenanocapacitor 18 into the environment of the energy-releasing nanoscaletransponder 10.

Several systems and methods have been used for transcutaneouslyinductively recharging an implantable medical device, as known in theart. Optionally, the electric charge of the nanocapacitor 18 can bemaintained, or the nanocapacitor 18 can be recharged through aninductance recharging unit. Inductive charging utilizing an externalelectromagnetic field is used to transfer energy from the chargingstation that sends energy through inductive coupling to thenanocapacitor 18 of the implanted energy-releasing carbon nanotubetransponder 10.

The inductance recharging unit makes use of a first induction coil tocreate an alternating electromagnetic field from within the chargingbase station. In an exemplary embodiment, the nanocapacitor 18 isprovided by the company SolRayo (Madison, Wis.). However it can bepurchased from other manufacturers. In this exemplary embodiment, thenanocapacitor 18 contains a coiled nanowire 24 a that constitutes asecond induction coil within the energy-releasing carbon nanotubetransponder 10. A coiled nanowire 24 a located inside the nanocapacitor18 constitutes a second induction coil within the energy-releasingcarbon nanotube transponder 10.

This coiled nanowire 24 a takes power from the electromagnetic field andconverts it back into electrical current to charge the nanocapacitor 18located inside the energy-releasing carbon nanotube transponder 10. Thetwo induction coils, i.e. the coiled nanowire 24 a of the nanocapacitor18, and the induction coil of the inductance recharging unit, inproximity combine to form an electrical transformer. In this exemplaryembodiment, the coiled nanowire 24 a contained in the nanocapacitor 18allows for the nanocapacitor 18 to be recharged. Optionally, the coilednanowire 24 a can also be used to externally trigger the nanocapacitor18 to discharge. This optional functionality of the coiled nanowire 24 acan be used to, for example, remotely receive an electromagnetic signalto trigger the release of electric energy from a plurality ofenergy-releasing carbon nanotube transponders 10 in a predeterminedsequence, independently of any other signal. Furthermore, the coilednanowire 24 a can optionally be used to exploit the versatility of apopulation of transponders to replay a sequence of neural code initiallycaptured by the transponders and transmitted to an external receiverusing the Radio Frequency Identification Device (RFID) capability of thecarbon nanotube transponder 10.

The charging base station has a shape appropriate to the placement ofthe energy-releasing carbon nanotube transponder 10, for example, whenan energy-releasing carbon nanotube transponder 10 is implanted into thebrain, an appropriate shape for the charging base station is, forexample, a hat, a helmet or a head scarf.

A carbon nanotube 12 is intrinsically either a conducting orsemi-conducting carbon-based material. Therefore, it carries electronsin the outer valence shell that by definition make it charged. In fact,carbon nanotubes have more robust and stable electrostatic charge than anatural polymer, like chitosan, which is very pH dependent. Therefore anelectric or magnetic field induced within the target tissue is onedriving force that can guide a carbon nanotube 12 or an energy-releasingcarbon nanotube transponder 10 through a tissue to a target location. Anexample of a suitable tissue is a brain tissue that is part of the CNStissue. Beyond guiding a nanodevice to the proper location, an electricor magnetic field can also be used to force an energy-releasing carbonnanotube transponder 10 into a dense tissue such as, for example, atumor mass or a scar in the brain. Accordingly, and depending on thetissue, it is optionally possible to use electrodes to generate anelectric field and guide the energy-releasing carbon nanotubetransponder 10 towards a target location. This optional guidingtechnique can be performed to optimize placement of an energy-releasingcarbon nanotube transponder 10 within a tissue. An energy-releasingcarbon nanotube transponder 10 can be guided by the electric fieldproduced for example by implanted intracranial electrodes. Suitableelectrodes are for example multi-contact extracellular stimulatingmicroelectrode probes (NeuroNexus Technologies, Inc., Ann Arbor, ML).

Optionally, the outer surface of the energy-releasing nanoscaletransponder 10 can be coated with biocompatible molecules to form abiocompatible coating 20, for example to improve cellular binding orbody tolerance towards the energy-releasing carbon nanotube transponder10. Both biodegradable polymers and non-biodegradable polymers can beused to coat the energy-releasing carbon nanotube transponder 10. Carbonnanotubes and carbon-rich nanocapacitors are considered biocompatible.It is the catalyst contaminants used to produce the nanotubes (e.g.,iron, nickel, yttrium) that are potentially toxic. Polymers such aspolylactic acid (PLA), polyglycolic acid (PGA) and poly lactideco-glycolide (PLGA) have a long standing history of use for medicalapplications. They meet the biological requirements of safety and arebiodegradable to non-toxic metabolites. They are also approved by theFDA for such use. These polymers are only three examples amongst othersof suitable biocompatible coating 20 for the energy-releasing carbonnanotube transponder 10. Another non-limiting example of biocompatiblecoating 20 for the energy-releasing carbon nanotube transponder 10 isthe natural polymer chitosan (i.e. a derivative of chitin fromcrustacean and insect exoskeletons). See Domb et al, Biodegradablepolymers as drug carrier systems. In: Polymeric Biomaterials, 2ndedition Dumitriu S (Ed). Marcel Dekker, New York pp 91-121 (2002).

The efficacy of treatment with the energy-releasing carbon nanotubetransponder 10 is assessed according to methods well known in the art todetermine for example the shrinkage of tumors, the destruction of cancercells, the reduction in the frequency of epileptic episodes, theabortion of seizures, the improvement of heart rhythms or whenapplicable methods such as tissue sectioning followed by tissue staining(e.g., Giemsa staining) can be used to visualize cell death and tissuedamage.

EXAMPLES

The present invention is further defined in the following examples. Itshould be understood that these examples, while indicating preferredembodiments of the invention, are given by way of illustration only.From the above discussion and these examples, one skilled in the art canascertain the essential characteristics of this invention, and withoutdeparting from the spirit and scope thereof, can make various changesand modifications of the invention to adapt it to various uses andconditions. The following examples are illustrative of the invention.

Example 1

In the first exemplary embodiment, tumor-specific nanosensors 16 arecreated to target brain cancer cells named glioblastoma multiforme(GBM). An exemplary marker is interleukin-13R-alpha2 (IL-13Ra2). Thenanosensor 16, i.e. SWCNT-IL-13Ra2, is formed by attaching at least onecarbon nanotube 12 using noncovalent functionalization, to the IL-13Ra2biomolecule ligand (i.e. IL-13) 14. See Teker, Bioconjugated carbonnanotubes for targeting cancer biomarkers, Materials Science Engineering153(1-3):83-87 (2008). The biomolecule ligand 14 specifically binds tothe IL-13Ra2 receptors located on the surface of GBM, but not to otherreceptors. Therefore, the biomolecule ligand 14 located onto the surfaceof the energy-releasing carbon nanotube transponder 10 allows for itsspecific binding onto GBM to minimize subsequent damage to healthynon-cancer cells.

When a biomolecule ligand 14 covalently attached to a carbon nanotube 12binds to its respective receptor, the conductivity of the carbonnanotube 12 has been shown to increase by two-to-ten orders ofmagnitude. A change in impedance of the functionalized carbon nanotube12 (i.e. carbon nanotube 12 linked with a biomolecule ligand of interest14 e.g. IL-13) can change its conductivity to allow discharging of thenanocapacitor 18.

Accordingly, upon the binding of the biomolecule ligand 14 to areceptor, the nanosensor 16 acts as a nanoswitch. The activation of thenanoswitch permits release of the electrical energy stored in thenanocapacitor 18 into the surrounding environment of theenergy-releasing carbon nanotube transponder 10, for example, onto thesurface of cancer cells that are then damaged or even destroyed.

In the first exemplary embodiment, the method described in the presentdisclosure comprises:

identifying brain cancer cells responsible for cancer to be treated;

determining a marker corresponding to said brain cancer cells;

providing a biomolecule ligand 14 specific to the marker;

binding the biomolecule ligand 14 to at least one carbon nanotube 12 toform a nanosensor 16;

connecting at least one nanosensor 16 to a nanocapacitor 18 to form anenergy-releasing carbon nanotube transponder 10;

optionally, coating the energy-releasing carbon nanotube transponder 10with a biocompatible coating 20;

optionally, binding a molecular label 22 to the energy-releasing carbonnanotube transponder 10;

providing a plurality of energy-releasing carbon nanotube transponders10;

determining an optimum electric charge to be provided to eachnanocapacitor 18 for the plurality of energy-releasing carbon nanotubetransponders 10 to deliver an electric charge to the brain cancer cellsin the range of between about 4 and about 30 microCoulombs/cm²;

storing the optimum electric charge into each nanocapacitor 18 of theplurality of energy-releasing carbon nanotube transponders 10;

placing the plurality of the energy-releasing carbon nanotubetransponders 10 proximately to the brain cancer cells;

automatically releasing the optimum electric charge from eachnanocapacitor 18 proximately to the brain cancer cells in response tothe binding of the biomolecule ligand 14 onto its receptor located ontothe surface of the brain cancer cells;

optionally, recharging the plurality of nanocapacitors 18 within theenergy-releasing carbon nanotube transponders 10 for allowing multipletreatments; and

assessing treatment efficacy with the plurality of energy-releasingcarbon nanotube transponders 10.

Example 2

In a second exemplary embodiment, a nanosensor 16 is created to detectdynamic alterations in the concentration of the neurotransmitterglutamate generated by neurons surrounding brain neoplastic cells. Suchmicroperturbations of glutamate concentration representing epileptiformactivity are used to trigger the release of electric energy from theenergy-releasing carbon nanotube transponder 10 into the directenvironment of the cells associated with epileptic episodes.

A nanosensor 16 formed by the attachment of a biomolecule ligand 14 to acarbon nanotube 12 can be introduced into one or more epileptic circuitsto detect changes during seizure activity (e.g., femtomolar increases inthe neurotransmitter glutamate correlates to an increased conductivityof at least one carbon nanotube 12 of the nanosensor 16). A detectionthreshold of the energy-releasing carbon nanotube transponder 10 can beused to discharge a nanocapacitor 18 to deliver direct stimulationtherapy to potentially stabilize epileptic circuit.

The nanosensor 16 is bound to a nanocapacitor 18 to form theenergy-releasing carbon nanotube transponder 10. In the energy-releasingcarbon nanotube transponder 10, at least one carbon nanotube 12 forms ananowire to conduct the electricity from the nanocapacitor 18 to thearea surrounding the energy-releasing carbon nanotube transponder 10.

In this second exemplary embodiment, the method described in the presentdisclosure comprises:

identifying dynamic alterations in the concentration of a chemical, forexample the neurotransmitter glutamate, that correlate with analteration in local electric fields;

alternatively, identifying a dynamic alteration in local electric fieldsthat is caused by an affliction to be treated;

identifying target cells related to the dynamic alteration in localelectric fields;

determining a marker corresponding to the target cells;

identifying a biomolecule ligand 14 specific to the marker of the targetcells to be treated;

binding the biomolecule ligand 14 to at least one carbon nanotube 12 toform a nanosensor 16;

connecting at least one said nanosensor 16 to a nanocapacitor 18 to forman energy-releasing carbon nanotube transponder 10;

optionally, coating the energy-releasing carbon nanotube transponder 10with a biocompatible coating 20;

optionally, binding a molecular label 22 to the energy-releasing carbonnanotube transponder 10;

providing a plurality of energy-releasing carbon nanotube transponders10;

determining an optimum electric charge to be provided to eachnanocapacitor 18 for the plurality of energy-releasing carbon nanotubetransponders 10 to deliver a biologically non-destructive electriccharge to the target cells in the range of between about 4 and about 20microCoulombs/cm²;

storing the optimum electric charge into each nanocapacitor 18 of theplurality of energy-releasing carbon nanotube transponders 10;

placing the plurality of energy-releasing carbon nanotube transponders10 proximately to the target cells;

automatically releasing the optimum electric charge from eachnanocapacitor proximately to the target cells in response to dynamicalterations in the concentration of, in this exemplary embodiment, theneurotransmitter glutamate;

optionally, recharging the plurality of nanocapacitors 18 within theenergy-releasing carbon nanotube transponders 10 for allowing multipletreatments; and

assessing treatment efficacy with the plurality of energy-releasingcarbon nanotube transponders 10.

Example 3

In a third exemplary embodiment, a carbon nanotube transponder 10 iscreated to react to dynamic alterations in the concentration of hydrogenions resulting from cardiac ischemic changes. Acute myocardial ischemiais triggered by insufficient blood flow to the heart. Acute myocardialischemia, and other heart conditions such as for example ventriculararrhythmias, decrease the level of oxygen and induce anaerobicmetabolism within cardiac tissue. Diseases such as, for example, acutemyocardial ischemia or ventricular arrhythmias are the directconsequences of a disregulation of the electrical conduction system ofthe heart.

To optimize stimulation of cardiac tissue, a plurality ofenergy-releasing carbon nanotube transponders 10 can be utilized totarget specific cardiac cells. Microperturbations in hydrogen ionsconcentration allow for the detection of anaerobic metabolism due to alack of oxygen within cardiac tissue. The energy-releasing carbonnanotube transponder 10, can be placed at various locations inside anappropriate heart tissue to trigger release of electrical energy used todefibrillate heart muscle syncytium and/or pacer cells in response tomicroperturbations in hydrogen ion concentrations.

In this third exemplary embodiment, placement of a plurality ofenergy-electric carbon nanotube transponders 10 within an appropriatetissue of the electrical conduction system of the heart, for example,the atrioventricular node or the sinus node, can trigger the release ofelectric energy from the energy-electric carbon nanotube transponder 10to alter the electrical propagation within the heart muscle of heartpatients suffering from for example acute myocardial ischemia orventricular arrhythmias.

A plurality of energy-electric carbon nanotube transponders 10 can beintroduced into one or more electrical conduction circuit of the heartto react to changes in hydrogen ions concentration during cardiacischemic changes (e.g., femtomolar increases in hydrogen ionsconcentration correlates with an increased conductivity of at least onecarbon nanotube 12). A detection threshold of the energy-releasingcarbon nanotube transponder 10 can be used to discharge a nanocapacitor18 to deliver direct stimulation therapy to the electrical conductioncircuit of the heart. In the energy-releasing carbon nanotubetransponder 10, at least one carbon nanotube 12 forms a nanowire toconduct the electricity from the nanocapacitor 18 to the areasurrounding the energy-releasing carbon nanotube transponder 10.

In this third exemplary embodiment, the method described in the presentdisclosure comprises:

identifying dynamic alterations in concentration of ions, for examplehydrogen ions, that correlate with an alteration in the electricalconduction system of the heart;

alternatively, identifying a dynamic alteration in the electricalconduction system of the heart that is caused by an affliction to betreated;

identifying target cells related to the dynamic alteration in theelectrical conduction system of the heart;

optionally, identifying a biomolecule ligand 14 specific to the cells ofa tissue to be treated;

optionally, binding the biomolecule ligand 14 to at least one carbonnanotube 12;

binding at least one the carbon nanotube 12 to a nanocapacitor 18 toform an energy-releasing carbon nanotube transponder 10;

optionally, coating the energy-releasing carbon nanotube transponder 10with a biocompatible coating 20;

optionally, binding a molecular label 22 to the energy-releasing carbonnanotube transponder 10;

providing a plurality of energy-releasing carbon nanotube transponders10;

determining an optimum electric charge to be provided to eachnanocapacitor 18 for the plurality of energy-releasing carbon nanotubetransponders 10 to deliver a biologically non-destructive electriccharge to the target cells in the range of between about 4 and about 20microCoulombs/cm²;

storing the optimum electric charge into each nanocapacitor 18 of theplurality of energy-releasing carbon nanotube transponders 10;

placing the plurality of energy-releasing carbon nanotube transponders10 proximately to the target cells;

automatically releasing the optimum electric charge from eachnanocapacitor proximately to the target cells in response to dynamicalterations in the concentration of, in this exemplary embodiment,hydrogen ions; or in response to dynamic alterations in the electricalconduction system of the heart that is caused by the affliction to betreated;

optionally, recharging the plurality of nanocapacitors 18 within theenergy-releasing carbon nanotube transponders 10 for allowing multipletreatments; and

assessing treatment efficacy with the plurality of energy-releasingcarbon nanotube transponders 10.

Example 4

In a fourth exemplary embodiment the optional molecular label 22 istechnetium (99 mTc) that can be used to check for the proper placementof an energy-releasing carbon nanotube transponder 10 or a component ofan energy-releasing carbon nanotube transponder 10 (e.g., carbonnanotube 12).

In this exemplary embodiment, the 99 mTc-carbon nanotube 12 scaffold issynthesized from amine functionalized water soluble CNT. The covalentattachment of multiple linker amine groups ofdiethylenetriaminepentaacetic (DTPA) to a carbon nanotubes 12 backboneis utilized as avid coupling sites for the chelator 6-hydrazinenicotinamide (HyNic) bound to 99 mTc. DTPA anhydride is highly solublein water and follows a simple conjugation chemistry to link two aminogroups at the carbon nanotubes 12 surface. The 99 mTc radioisotope isobtained as technetium pertechnetate (99 mTcO₄ ⁻) (CovidienPharmaceuticals, Hazelwood, Mo.) as an aqueous solution and used withoutfurther purification. 99 mTc decays by isomeric transition with aphysical half-life of 6 hours. Therefore, this molecular label 22 can beeasily placed onto carbon nanotube 12 of the energy-releasing carbonnanotube transponder 10 prior to use, in vivo. Thanks to its molecularlabel 22, the precise location of an energy-releasing carbon nanotubetransponder 10 can be determined and visualized by using for example aSingle photon emission computed tomography (SPECT) scanner (e.g.inSPira® SPECT scanner, NeuroLogica Corporation, Danvers, Mass.).

An exemplary protocol to form the 99 mTc-carbon nanotube 12 conjugate isdirectly derived from the protocol published by Wu et al. (2009). Puresemiconducting SWNT (NanoIntegris, Inc, Skokie, Ill.) (5.5 mg, 2.75μmol) at a length of 200-500 nm is dissolved in 1 ml of anhydrous DMSOand neutralized with diisopropylethylamine (DIEA) (1 μl; 5.9 μmol). DTPAdianhydride (590 μg; 1.65 μmol) is added, and the mixture is stirred for3 hr at room temperature. The DMSO solution is diluted with deionizedwater (5 ml) and lyophilized twice in a VACUFUGE® (Eppendorf NorthAmerica, Hauppauge, N.Y.). The crude DTPA-CNT derivative isre-precipitated from methanol/diethyl ether several times andlyophilized again from water. The number of the free amino groupsremaining on the CNT is measured by the quantitative Kaiser test. Aratio of unreacted amines is determined by calculating the ratio betweenthe number of amino groups on this CNT and the amount of DTPA used. As aresult, the CNT is functionalized with amine side-groups. Thefunctionalized CNT is obtained in powder form for complexation withtechnetium (99 mTc), itself an example of molecular label 22.

CNT functionalized with amine side-groups is labeled with the molecularlabel 22 i.e. 99 mTc in this example using the HyNic spacer.Succinimidyl 6-hydrozinium nicotinate (SHNH) is used to linkHyNic-DTPA-CNT with 99 mTcO₄ ⁻. SHNH is a bifunctional aromatichydrazine linker that forms a stable bis-aryl hydrazone bond between 99mTcO₄ ⁻ and the HyNic-DTPA-CNT complex. 5 ml of HyNic-DTPA-CNT issuspended in 1000 μl of SoluLink modification buffer (pH 7.4) (Solulink,Inc., San Diego, Calif.). A stock solution of SHNH is prepared inanhydrous DMSO for immediate use by dissolving 2-4 mg of SHNH in 100 μlDMSO. The requisite volume of SHNH/DMSO is added to the HyNic-DTPA-CNTsolution and incubated for 120 minutes. The DMSO buffer is exchangedwith 0.1M sodium phosphate, and 0.15M sodium chloride, (pH 6.0) usingZeba Desalt spin columns (Thermo Scientific, Rockford, Ill.). Theresulting solution is injected into a vial containing an aqueoussolution of 99 mTcO₄ ⁻ (Covidien Pharmaceuticals, Hazelwood, Mo.) toform the molecular label 22-carbon nanotube 12 conjugate.

Example 5

In a fifth exemplary embodiment a molecular ligand 14 is interleukin-13(IL-13), however, an example of a suitable molecular ligand 14 is notlimited to IL-13. In this exemplary embodiment, the IL-13-carbonnanotube 12 scaffold is synthesized from amine functionalized watersoluble CNT. The covalent attachment of multiple linker amine groups ofdiethylenetriaminepentaacetic (DTPA) to a carbon nanotubes 12 backboneis utilized as avid coupling sites for the chelator 6-hydrazinenicotinamide (HyNic) bound to IL-13. DTPA anhydride is highly soluble inwater and follows a simple conjugation chemistry to link two aminogroups at the carbon nanotubes 12 surface. To bind IL-13 to carbonnanotube 12, lyophilized human recombinant IL-13 (ProSpec-TanyTechnoGene Ltd, Rehovot, Israel) is acquired as a singlenon-glycosylated polypeptide containing 112 amino acids with a molecularweight of 12 kDa. This freeze-dried powder is reconstituted in sterilewater at 10 ug in 1 ml. This solution is mixed with the a HyNic-DTPA-CNTcomplex, as prepared in Example 4, for 1 hr at room temperature to forma biomolecule ligand 14-carbon nanotube 12 complex. Optionally, thisIL-13 solution is mixed with a molecular label 22-carbon nanotube 12conjugate such as 99 mTc-HyNic-DTPA-CNT complex, as prepared in Example4, for 1 hr at room temperature to form a molecular label 22-biomoleculeligand 14-carbon nanotube 12 complex. After this simple mixing step,proteins have been shown to self-assemble and adhere to the nanotubesidewalls remaining bound under ambient conditions. See Azamian et al,Bioelectrochemical single-walled carbon nanotubes. J Am Chem Soc.124(43):12664-5 (2002).

Example 6

In a sixth exemplary embodiment, a plurality of energy-releasing carbonnanotube transponder 10 is placed within the white matter of a humanbrain to propagate a non-destructive electric charge in an epileptictissue to subsequently abort epileptic seizures. In this exemplaryembodiment, an energy-releasing carbon nanotube transponder 10 islabeled with technetium (99 mTc), a molecular label 22. Thanks to thismolecular label 22, the precise location of an energy-releasing carbonnanotube transponder 10 can be determined and visualized by using forexample single photon emission computed tomography (SPECT) scanner (e.g.inSPira® SPECT scanner, NeuroLogica Corporation, Danvers, Mass.). Theoptimum placement of the energy-releasing carbon nanotube transponder 10is determined by using a combination of four techniques known in theart. The first technique is subtracted-ictal SPECT co-registered to MRI.The second technique is subtracted post-ictal diffusion tensor imaging(spiDTI) that is used to assess anatomically specific changes infractional anisotropy (FA) compared to baseline axonal water diffusionduring the early post-ictal period of a focal-onset complex partialseizure. The third technique employs finite element method (FEM)modeling to predict the maximal electric field magnitude immediatelysurrounding a plurality of carbon nanotube transponder 10. The volume ofcortical activation (VOCA) is calculated from the greatest magnitude ofthe electric field immediately surrounding a plurality of carbonnanotube transponder 10. The fourth technique is diffusion tensortractography. Once the optimum placement is determined, a plurality ofenergy-releasing carbon nanotube transponder 10 is precisely positionedin the epileptic tissue using NeuroNexus fluidic microelectrode probesfrom (NeuroNexus Technologies, Inc., Ann Arbor, Mich.). A plurality ofenergy-releasing carbon nanotube transponders 10 can be electricallycharged using an inductance-based charging base station that has anappropriate shape i.e. that shape of a helmet. Once in the brain, theplurality of energy-releasing carbon nanotube transponder 10 can beelectrically discharged. In this exemplary embodiment, the plurality ofenergy-releasing carbon nanotube transponder 10 propagates anon-destructive charge of 9.1 microCoulombs/cm² in the epileptic tissueof a human patient. Once discharged, the energy-releasing carbonnanotube transponder 10 is recharged by inductance, as known in the art,for performing multiple treatments with electric stimulations of theepileptic tissue to abort epileptic seizures.

Example 7

In a seventh exemplary embodiment, the energy-releasing carbon nanotubetransponder 10 is labeled with fluorescein i.e. the optional molecularlabel 22. This exemplary embodiment allows for in vitro characterizationof the electric field that is optionally required to guide the migrationof the energy-releasing carbon nanotube transponder 10. Once defined byusing this exemplary embodiment, this electric field is recreated in ofa human brain tissue using NeuroNexus fluidic microelectrode probes from(NeuroNexus Technologies, Inc., Ann Arbor, Mich.). Since this electricfield is biocompatible, it allows for a controlled migration of aplurality of energy-releasing carbon nanotube transponder 10 in vivo, inthe brain of an epileptic patient. In this exemplary embodiment a 0.5%agarose gel produces a porosity similar to that of a human brain. Toallow for subsequent fluorescence labeling of SWNT, a plurality ofcarbon nanotubes 12 is first oxidized according to the following method:5 mg dry semiconducting SWNT 90-95% purity (NanoIntegris, Inc, Skokie,Ill.) are treated with 8M concentrated solution of sulfuric and nitricacid. The SWNT are then sonicated for 5 hours at 60° C. in an ultrasonicbath (Model FS60D, Fisher Scientific, part of Thermo Fisher Scientific,Rockford, Ill.) to introduce carboxylic acid groups on the SWNT surface.Carboxylation allows for covalent bonding of amide linkages that areused to functionalize SWNT. Carboxylated SWNT are centrifuged at 3.5 krmp for 10 min. The supernatants is collected and added to 150 mL ofcold deionized distilled water. The supernatant is then filtered througha 0.22 μm pore size polycarbonate filter paper (i.e. Isopore Membrane,polycarbonate, Hydrophilic, 0.22 μm, Cat. No. GTTP02500, Millipore,Billerica, Mass.). The filtrand is washed with distilled water until noresidual acid is present. The filtrand is then dispersed in ethanol.

The filtrand is dried in a vacuum oven at (−20 in. Hg) 80° C. overnight.At least one carbon nanotube 12 of an energy-releasing carbon nanotubetransponder 10 is labeled with fluorescein according to the followingmethod:

One milligram of the oxidized semiconducting nanotubes 12 is treatedwith 0.1M 2-(N-morpholino) ethanesulfonic acid (Fisher Scientific)(IVIES buffer), 10 mM 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide(EDC) (Sigma Aldrich, St Louis, Mo.) and 1MFluorescein-5-thiosemicarbazide (FITC) (Sigma Aldrich). This mixture isthen dispersed by sonication for 5 min and stirred for 3 h and deionizedwater is subsequently used to dilute this mixture. The diluted mixtureis then centrifuged at 7.0 k rmp for 10 min. The supernant with freeFITC is removed and the process is repeated until all free FITC isremoved.

Each step of the process of chemical functionalization of the SWNT isverified, for example, by Fourrier Transform Infrared Spectroscopy(FTIR). In this exemplary embodiment, FTIR is used to verify each stepof the SWNT chemical functionalization process according to thefollowing analytical procedure: A plurality of oxidized carbon nanotubes12 is dried in a vacuum oven (−20 in. Hg) at 80° C. overnight prior toFTIR. The FTIR sample is prepared by grounding thoroughly SWNT withpotassium bromide (KBr) at 1-2 wt % and the resulting powder is pressedinto a transparent pellet using hydraulic press. A plurality offluorescein labeled carbon nanotubes 12 is dried in a vacuum oven (−20in. Hg) at 80° C. overnight prior to FTIR. The FTIR sample is preparedby first grounding thoroughly 1-2 wt % of KBr. Dry fluorescein labeledsamples are then treated with dichloromethane and sonicated for 5 min.Thereafter, this solution is poured into grounded KBr and dried in anoven for 10 min. Upon completion, the samples are grounded and theresulting powder is pressed into a transparent pellet using a hydraulicpress.

To further verify the functionality of the fluorescence labeling of aplurality of carbon nanotubes 12, and to characterize the electric fieldthat is optionally required to guide the migration of a plurality ofenergy-releasing carbon nanotube transponder 10 labelled withfluorescein, the migration of these carbon nanotubes 12 is monitoredthrough a 0.5% agarose gel producing a porosity similar to that ofbrain. To that end, four electrodes are arranged in a quadripolarconfiguration according to methods already known in the art. These fourelectrodes are constructed with platinum/iridium wires and contacts areattached to a polycarbonate culture dish lid in a cubic and a non-cubic,tetrad orientation. In a cubic orientation one pair of electrodes isdirectly facing a second pair of electrode so that the four electrodesform a perfect square onto the surface of the agarose gel. In anon-cubic orientation, only one electrode of a first pair of electrodesis directly facing a second electrode of the second pair of electrode sothat the four electrodes do not form a perfect square onto the surfaceof the agarose gel but rather form a diamond shape. 0.2 M sodiumphosphate and 0.1 M citric acid buffer (Sigma Aldrich) at pH 6.0 areused to prepare a 0.5% agarose Type VII (Sigma Aldrich) gel. Theelectrode copper tips are placed at a depth of 8 mm in a 10 mm thick0.5% agarose gel perpendicular to the gel surface prior to gel curing.Prior to gel curing injection loading wells are made by placing a 10 μLpipette tip in the gel. Two wells are created adjacent to twoneighboring electrodes of a first pair of electrodes, and a third wellis made equidistant between the two electrodes of the opposite secondpair of electrodes. The stainless steel endings are connected to aconstant current unit (Grass Technologies, West Warwick, R.I.). Thissetup is connected to a stimulus isolation unit (Grass Technologies)which in turn is controlled by an S88 stimulator (Grass Technologies).The charge of each electrode is opposite of the adjacent electrodearranged in an alternating manner. 1.5 μL of fluorescein labeled carbonnanotubes 12 or 1.5 μL of a plurality of energy-releasing carbonnanotube transponder 10 labelled with fluorescein is injected into thepreviously prepared agarose gel wells, in the well equidistant from thetwo electrodes. 0.2 M sodium phosphate and 0.1 M citric acid buffer atpH 6 are then injected on the gel surface to equalize the chargedistribution and cool the gel.

With electrodes in a cubic orientation, an alternating (AC) electricfield is applied for 3 h with the parameters 100 V, 5 mA, 1 Hz, 10 mspulse width. In parallel, a control without electric field is preparedin the same manner.

With electrodes in a non-cubic orientation, an alternating (AC) electricfield is applied for 3 h with the parameters 100 V, 5 mA, 1 Hz, however,a charge imbalance is introduced by applying two electric fields withtwo different pulse widths. One first pair of adjacent electrodesreceives a pulse field of 50 ms while the second pair of electrodesreceives a pulse field of 10 ms. In this non-cubic configuration, thewell where the injection takes place, equidistant from the twoelectrodes, receives a pulse field of 50 ms. The fluorescence of thisseventh exemplary embodiment is visualized using a Blue ViewTransilluminator (Vernier, Beaverton, Oreg.). This exemplary embodimentallows for the characterization of a biocompatible electric field thatis delivered in a human brain tissue to optionally guide the migrationof the energy-releasing carbon nanotube transponder 10. According tothis exemplary embodiment, a preferred electrode configuration in vitroas well as in vivo is a quadripolar configuration that allows for thecontrolled migration of a plurality of carbon nanotube transponder 10through the electric field generated between the four electrodes.Methods already known in the art allow for the direct transition from invitro to in vivo settings with little modifications. In vivo, theenergy-releasing carbon nanotube transponder 10 is preferentiallylabeled with technetium (99 mTc), a molecular label 22, as exemplifiedin example 6.

1. An energy-releasing carbon nanotube transponder responsive to changesin a chemical concentration or electrical property of its environment,and wherein said energy-releasing carbon nanotube transponder is up to500 nanometers in diameter for delivering electrical energy to acellular tissue comprising: (a) at least one carbon nanotube; and (b) ananocapacitor connected to the first end of said at least one carbonnanotube, wherein said nanocapacitor is capable of storing apredetermined amount of electric energy in the form of a mean chargedensity in the range of between about 1.2×10⁻⁵ and about 2.4×10⁻⁵Coulombs/cm², and said at least one carbon nanotube being connected tosaid nanocapacitor acts as a nanoswitch for releasing said predeterminedamount of electrical energy to said cellular tissue in response to achange in the environment of said energy-releasing carbon nanotubetransponder, and wherein a plurality of said energy-releasing carbonnanotube transponders is capable of releasing a biologicallynon-destructive electric charge in the range of between about 4 andabout 20 microCoulombs/cm² to said cellular tissue.
 2. Anenergy-releasing carbon nanotube transponder responsive to changes in achemical concentration or electrical property of its environment, andwherein said energy-releasing carbon nanotube transponder is up to 500nanometers in diameter for delivering electrical energy to a cellulartissue comprising: (a) at least one carbon nanotube; and (b) ananocapacitor connected to the first end of said at least one carbonnanotube, wherein said nanocapacitor is capable of storing apredetermined amount of electric energy in the form of a mean chargedensity mean charge density in the range of between about 1.2×10⁻⁵ andabout 2.4×10⁻⁵ Coulombs/cm², and said at least one carbon nanotube beingconnected to said nanocapacitor acts as a nanoswitch for releasing saidpredetermined amount of electrical energy to said cellular tissue inresponse to a change in the environment of said energy-releasing carbonnanotube transponder, and wherein a plurality of said energy-releasingcarbon nanotube transponders is capable of releasing a biologicallydestructive electric charge in the range of between about 21 and about30 microCoulombs/cm² and preferably about 23 microCoulombs/cm² to saidcellular tissue.
 3. The energy-releasing carbon nanotube transponderaccording to claim 1 or 2, further comprising a coiled nanowire locatedinside said nanocapacitor.
 4. The energy-releasing carbon nanotubetransponder according to claim 1 or 2, further comprising a coilednanowire located outside said nanocapacitor.
 5. The energy-releasingcarbon nanotube transponder according to claim 1 or 2, furthercomprising a biocompatible coating on the outer surface of saidenergy-releasing carbon nanotube transponder.
 6. The energy-releasingcarbon nanotube transponder according to claim 5, wherein saidbiocompatible coating is a material selected from the group consistingof polylactic acid (PLA), polyglycolic acid (PGA), poly lactideco-glycolide (PLGA) and chitosan.
 7. The energy-releasing carbonnanotube transponder according to claim 1 or 2, further comprising amolecular label linked to a free end of at least one said carbonnanotube, the free end of said carbon nanotube being distal from saidnanocapacitor.
 8. The energy-releasing carbon nanotube transponderaccording to claim 7, wherein said molecular label is a materialselected from the group consisting of technetium and indium-111.
 9. Theenergy-releasing carbon nanotube transponder according to claim 1 or 2,further comprising a biomolecule ligand linked to a free end of at leastone said carbon nanotube, the free end of said carbon nanotube beingdistal from said nanocapacitor.
 10. The energy-releasing carbon nanotubetransponder according to claim 9, wherein said biomolecule ligand isInterleukin-13 (IL-13).
 11. The energy-releasing carbon nanotubetransponder according to claim 9, wherein said biomolecule ligand isglutamate.
 12. The energy-releasing carbon nanotube transponderaccording to claim 9 in which the binding of said biomolecule ligand toa cellular receptor changes an electronic characteristic of said carbonnanotube, and wherein a modification of said electronic characteristicinduces the release of the electrical energy stored in saidnanocapacitor into the environment of said energy-releasing carbonnanotube transponder through said carbon nanotube that acts as ananowire.
 13. The energy-releasing carbon nanotube transponder as in anyone of claims 1, and 2, in which changes in said chemical concentrationin the environment of said energy-releasing carbon nanotube transpondermodify an electronic characteristic of said carbon nanotube, and whereina modification of said electronic characteristic induces the release ofthe electrical energy stored in said nanocapacitor into the environmentof said energy-releasing carbon nanotube transponder through said carbonnanotube that acts as a nanowire.
 14. The energy-releasing carbonnanotube transponder according to claim 13, in which said chemicalconcentration is glutamate concentration.
 15. The energy-releasingcarbon nanotube transponder according to claim 13, in which saidchemical concentration is hydrogen ions concentration.
 16. Theenergy-releasing carbon nanotube transponder as in any one of claims 1,and 2, in which changes in said electrical property in the environmentof said energy-releasing carbon nanotube transponder modify anelectronic characteristic of said carbon nanotube, and wherein amodification of said electronic characteristic induces the release ofthe electrical energy stored in said nanocapacitor into the environmentof said energy-releasing carbon nanotube transponder through said carbonnanotube that acts as a nanowire.
 17. A method of using a plurality ofenergy-releasing carbon nanotube transponders to treat medicalafflictions selected from the group consisting of cancer, epilepsy,brain seizures, ventricular arrhythmias and myocardial ischemia in humanand non-human patients comprising: (a) identifying target cellsresponsible for a medical affliction to be treated; (b) predeterminingan optimum electric charge to store into a nanocapacitor of anenergy-releasing carbon nanotube transponder; (c) storing said optimumelectric charge into said nanocapacitor of said energy-releasing carbonnanotube transponder; (d) placing a plurality of said energy-releasingcarbon nanotube transponders proximately to said target cells; (e)automatically releasing said optimum electric charge from saidnanocapacitor into the environment of said plurality of energy-releasingcarbon nanotube transponders in response to an environmental stimuluscomprising changes in a chemical concentration, and changes in anelectrical property of the environment of said plurality ofenergy-releasing carbon nanotube transponders; and (f) assessingtreatment efficacy with said plurality of energy-releasing carbonnanotube transponders.
 18. The method according to claim 17, furthercomprising binding a biomolecule ligand to at least one carbon nanotubeto form a nanosensor.
 19. The method according to claim 17, furthercomprising: (a) binding a molecular label to at least one said carbonnanotube; and (b) tracking said energy-releasing carbon nanotubetransponder by detecting said molecular label.
 20. The method accordingto claim 17, further comprising coating the outer surface of saidenergy-releasing carbon nanotube transponder with a biocompatiblecoating.
 21. The method according to claim 17, further comprisingrecharging each said nanocapacitor within said plurality ofenergy-releasing carbon nanotube transponders for allowing multipletreatments.
 22. The method according to claim 17, further comprisingguiding said plurality of energy-releasing carbon nanotube transpondersthrough an electric field.
 23. A method of using a plurality ofenergy-releasing carbon nanotube transponders to treat brain cancer inhuman and non-human patients by delivering a biologicallynon-destructive electric charge comprising: (a) identifying brain cancercells responsible for cancer to be treated; (b) determining a markercorresponding to said brain cancer cells; (c) providing a biomoleculeligand specific to said marker; (d) binding said biomolecule ligandselected from a group comprising IL-13 to at least one said carbonnanotube to form a nanosensor; (e) connecting at least one saidnanosensor to a nanocapacitor to form an energy-releasing carbonnanotube transponder; (f) providing a plurality of said energy-releasingcarbon nanotube transponders; (g) determining an optimum electric chargeto be provided to each said nanocapacitor for a plurality of saidenergy-releasing carbon nanotube transponders to deliver a biologicallynon-destructive electric charge to said brain cancer cells in the rangeof between about 4 and about 20 microCoulombs/cm²; (h) storing saidoptimum electric charge into each said nanocapacitor of said pluralityof said energy-releasing carbon nanotube transponders; (i) placing saidplurality of said energy-releasing carbon nanotube transpondersproximately to said brain cancer cells; (j) automatically releasing saidoptimum electric charge from said nanocapacitor proximately to saidbrain cancer cells in response to an environmental stimulus comprisingthe binding of said biomolecule ligand onto its receptor located ontothe surface of said brain cancer cells and changes in an electricalproperty of the environment of said plurality of energy-releasing carbonnanotube transponders; and (k) assessing treatment efficacy with saidplurality of energy-releasing carbon nanotube transponders.
 24. Themethod according to claim 23, further comprising: (a) binding amolecular label selected from the group consisting of technetium andindium-111 to said energy-releasing carbon nanotube transponder; and (b)tracking said energy-releasing carbon nanotube transponder by detectingsaid molecular label.
 25. The method according to claim 23, furthercomprising coating the outer surface of said energy-releasing carbonnanotube transponder with a biocompatible coating selected from thegroup consisting of polylactic acid (PLA), polyglycolic acid (PGA), polylactide co-glycolide (PLGA) and chitosan.
 26. The method according toclaim 23, further comprising recharging each said nanocapacitor withinsaid plurality of energy-releasing carbon nanotube transponders forallowing multiple treatments.
 27. The method according to claim 23,further comprising guiding said plurality of energy-releasing carbonnanotube transponders through an electric field.
 28. A method of using aplurality of energy-releasing carbon nanotube transponders to treatbrain cancer in human and non-human patients by delivering abiologically destructive electric charge comprising: (a) identifyingbrain cancer cells responsible for cancer to be treated; (b) determininga marker corresponding to said brain cancer cells; (c) providing abiomolecule ligand specific to said marker; (d) binding said biomoleculeligand selected from a group comprising IL-13 to at least one saidcarbon nanotube to form a nanosensor; (e) connecting at least one saidnanosensor to a nanocapacitor to form an energy-releasing carbonnanotube transponder; (f) providing a plurality of said energy-releasingcarbon nanotube transponders; (g) determining an optimum electric chargeto be provided to each said nanocapacitor for said plurality of saidenergy-releasing carbon nanotube transponders to deliver a biologicallydestructive electric charge to said brain cancer cells in the range ofbetween about 21 and about 30 microCoulombs/cm² and preferably about 23microCoulombs/cm²; (h) storing said optimum electric charge into eachsaid nanocapacitor of said plurality of said energy-releasing carbonnanotube transponders; (i) placing said plurality of saidenergy-releasing carbon nanotube transponders proximately to said braincancer cells; (j) automatically releasing said optimum electric chargefrom said nanocapacitor proximately to said brain cancer cells inresponse to an environmental stimulus comprising the binding of saidbiomolecule ligand onto its receptor located onto the surface of saidbrain cancer cells and changes in an electrical property of theenvironment of said plurality of energy-releasing carbon nanotubetransponders; and (k) assessing treatment efficacy with said pluralityof energy-releasing carbon nanotube transponders.
 29. The methodaccording to claim 28, further comprising: (a) binding a molecular labelselected from the group consisting of technetium and indium-111 to saidenergy-releasing carbon nanotube transponder; and (b) tracking saidenergy-releasing carbon nanotube transponder by detecting said molecularlabel.
 30. The method according to claim 28, further comprising coatingthe outer surface of said energy-releasing carbon nanotube transponderwith a biocompatible coating selected from the group consisting ofpolylactic acid (PLA), polyglycolic acid (PGA), poly lactideco-glycolide (PLGA) and chitosan.
 31. The method according to claim 28,further comprising recharging each said nanocapacitor within saidplurality of energy-releasing carbon nanotube transponders for allowingmultiple treatments.
 32. The method according to claim 28, furthercomprising guiding said plurality of energy-releasing carbon nanotubetransponders through an electric field.
 33. A method of using aplurality of energy-releasing carbon nanotube transponders to treatepilepsy in human and non-human patients by delivering a biologicallynon-destructive electric charge comprising: (a) identifying dynamicalterations in the concentration of a chemical, selected from a groupcomprising the neurotransmitter glutamate, that correlate with analteration in local electric fields; (b) identifying target cellsresponsible for epilepsy to be treated; (c) determining a markercorresponding to said target cells; (d) providing a biomolecule ligandspecific to said marker; (e) binding said biomolecule ligand selectedfrom a group comprising glutamate to at least one said carbon nanotubeto form a nanosensor; (f) connecting at least one said nanosensor to ananocapacitor to form an energy-releasing carbon nanotube transponder;(g) providing a plurality of said energy-releasing carbon nanotubetransponders; (h) determining an optimum electric charge to be providedto each said nanocapacitor for said plurality of said energy-releasingcarbon nanotube transponders to deliver a biologically non-destructiveelectric charge to said target cells in the range of between about 4 andabout 20 microCoulombs/cm²; (i) storing said optimum electric chargeinto each said nanocapacitor of said plurality of said energy-releasingcarbon nanotube transponders; (j) placing said plurality ofenergy-releasing carbon nanotube transponders proximately to said targetcells; (k) automatically releasing said optimum electric charge fromsaid nanocapacitor proximately to said target cells in response to anenvironmental stimulus comprising binding of said biomolecule ligandonto its receptor located onto the surface of said target cells, changesin an electrical property of the environment of said plurality ofenergy-releasing carbon nanotube transponders and, said dynamicalterations; and (l) assessing treatment efficacy with said plurality ofenergy-releasing carbon nanotube transponders.
 34. The method accordingto claim 33, further comprising: (a) binding a molecular label selectedfrom the group consisting of technetium and indium-111 to saidenergy-releasing carbon nanotube transponder; and (b) tracking saidenergy-releasing carbon nanotube transponder by detecting said molecularlabel.
 35. The method according to claim 33, further comprising coatingthe outer surface of said energy-releasing carbon nanotube transponderwith a biocompatible coating selected from the group consisting ofpolylactic acid (PLA), polyglycolic acid (PGA), poly lactideco-glycolide (PLGA) and chitosan.
 36. The method according to claim 33,further comprising recharging each said nanocapacitor within saidplurality of energy-releasing carbon nanotube transponders for allowingmultiple treatments.
 37. The method according to claim 33, furthercomprising guiding said plurality of energy-releasing carbon nanotubetransponders through an electric field.
 38. A method of using aplurality of energy-releasing carbon nanotube transponders to stabilizethe electrical epileptic circuit to abort seizures without injuringbrain cells comprising: (a) identifying dynamic alterations in theconcentration of a chemical, selected from a group comprising theneurotransmitter glutamate, that correlate with an alteration in localelectric fields; (b) identifying target cells responsible for epilepsyto be treated; (c) providing a plurality of energy-releasing carbonnanotube transponders; (d) determining an optimum electric charge to beprovided to each of said nanocapacitor for said plurality of saidenergy-releasing carbon nanotube transponders to deliver a biologicallynon-destructive electric charge to said target cells in the range ofbetween about 4 and about 20 microCoulombs/cm²; (e) storing said optimumelectric charge into each said nanocapacitor of said plurality of saidenergy-releasing carbon nanotube transponders; (f) placing saidplurality of the energy-releasing carbon nanotube transpondersproximately to said target cells; (g) automatically releasing saidelectric charge from said nanocapacitor proximately to said target cellsin response to an environmental stimulus comprising changes in anelectrical property of the environment of said plurality ofenergy-releasing carbon nanotube transponders and, said dynamicalterations; and (h) assessing treatment efficacy with said plurality ofenergy-releasing carbon nanotube transponders.
 39. The method accordingto claim 38, further comprising: (a) binding a molecular label selectedfrom the group consisting of technetium and indium-111 to saidenergy-releasing carbon nanotube transponder; and (b) tracking saidenergy-releasing carbon nanotube transponder by detecting said molecularlabel.
 40. The method according to claim 38, further comprising coatingthe outer surface of said energy-releasing carbon nanotube transponderwith a biocompatible coating selected from the group consisting ofpolylactic acid (PLA), polyglycolic acid (PGA), poly lactideco-glycolide (PLGA) and chitosan.
 41. The method according to claim 38,further comprising recharging each said nanocapacitor within saidplurality of energy-releasing carbon nanotube transponders for allowingmultiple treatments.
 42. The method according to claim 38, furthercomprising guiding said plurality of energy-releasing carbon nanotubetransponders through an electric field.
 43. A method of using aplurality of energy-releasing carbon nanotube transponders to stabilizethe electrical conduction system of the heart comprising: (a)identifying dynamic alterations in the concentration of chemical ionsselected from a group comprising hydrogen ions, that correlate with analteration in the electrical conduction system of the heart; (b)identifying target cells responsible for the alteration in saidelectrical conduction system of the heart; (c) providing a plurality ofenergy-releasing carbon nanotube transponders; (d) determining anoptimum electric charge to be provided to each said nanocapacitor forsaid plurality of said energy-releasing carbon nanotube transponders todeliver a biologically non-destructive electric charge to said targetcells in the range of between about 4 and about 20 microCoulombs/cm²;(e) storing said optimum electric charge into each said nanocapacitor ofsaid plurality of said energy-releasing carbon nanotube transponders;(f) placing said plurality of the energy-releasing carbon nanotubetransponders proximately to said target cells; (g) automaticallyreleasing said electric charge from said nanocapacitor proximately tosaid target cells in response to an environmental stimulus comprisingchanges in an electrical property of the environment of said pluralityof energy-releasing carbon nanotube transponders and, said dynamicalterations; and (h) assessing treatment efficacy with said plurality ofenergy-releasing carbon nanotube transponders.
 44. The method accordingto claim 43, further comprising: (a) binding a molecular label selectedfrom the group consisting of technetium and indium-111 to saidenergy-releasing carbon nanotube transponder; and (b) tracking saidenergy-releasing carbon nanotube transponder by detecting said molecularlabel.
 45. The method according to claim 43, further comprising coatingthe outer surface of said energy-releasing carbon nanotube transponderwith a biocompatible coating selected from the group consisting ofpolylactic acid (PLA), polyglycolic acid (PGA), poly lactideco-glycolide (PLGA) and chitosan.
 46. The method according to claim 43,further comprising recharging each said nanocapacitor within saidplurality of energy-releasing carbon nanotube transponders for allowingmultiple treatments.
 47. The method according to claim 43, furthercomprising guiding said plurality of energy-releasing carbon nanotubetransponders through an electric field.
 48. A method of using aplurality of energy-releasing carbon nanotube transponders to deliver asequence of a biologically non-destructive electric charge in the rangeof between about 4 and about 20 microCoulombs/cm² to target cells. (a)identifying target cells; (b) defining a predetermined sequence toremotely trigger a plurality of energy-releasing carbon nanotubetransponders by remotely applying an electromagnetic signal to saidplurality of energy-releasing carbon nanotube transponders; (c)providing said plurality of energy-releasing carbon nanotubetransponders; (d) determining an optimum electric charge to be providedto each nanocapacitor for said plurality of said energy-releasing carbonnanotube transponders to deliver a biologically non-destructive electriccharge to said target cells in the range of between about 4 and about 20microCoulombs/cm²; (e) storing said optimum electric charge into eachsaid nanocapacitor of said plurality of said energy-releasing carbonnanotube transponders; (f) placing said plurality of theenergy-releasing carbon nanotube transponders proximately to said targetcells; (g) remotely applying said electromagnetic signal to release saidoptimum electric charge from said nanocapacitor proximately to saidtarget cells; and (h) assessing treatment efficacy with said pluralityof energy-releasing carbon nanotube transponders.
 49. A method of usinga plurality of energy-releasing carbon nanotube transponders to delivera sequence of a biologically destructive electric charge in the range ofbetween about 21 and about 30 microCoulombs/cm² and preferably about 23microCoulombs/cm² to target cells. (a) identifying target cells; (b)defining a predetermined sequence to remotely trigger a plurality ofenergy-releasing carbon nanotube transponders by remotely applying anelectromagnetic signal to said plurality of energy-releasing carbonnanotube transponders; (c) providing said plurality of energy-releasingcarbon nanotube transponders; (d) determining an optimum electric chargeto be provided to each of said nanocapacitor for said plurality of saidenergy-releasing carbon nanotube transponders to deliver a biologicallydestructive electric charge to said target cells in the range of betweenabout 21 and about 30 microCoulombs/cm² and preferably about 23microCoulombs/cm²; (e) storing said optimum electric charge into eachsaid nanocapacitor of said plurality of said energy-releasing carbonnanotube transponders; (f) placing said plurality of theenergy-releasing carbon nanotube transponders proximately to said targetcells; (g) remotely applying said electromagnetic signal to release saidoptimum electric charge from said nanocapacitor proximately to saidtarget cells; and (h) assessing treatment efficacy with said pluralityof energy-releasing carbon nanotube transponders.
 50. The methodaccording to claim 48 or 49, further comprising: (a) determining amarker corresponding to said target cells; (b) providing a biomoleculeligand specific to said marker; (c) binding said biomolecule ligandselected to at least one said carbon nanotube to form a nanosensor; and(d) connecting at least one said nanosensor to a nanocapacitor.
 51. Themethod according to claim 48 or 49, further comprising: (a) binding amolecular label selected from the group consisting of technetium andindium-111 to said energy-releasing carbon nanotube transponder; and (b)tracking said energy-releasing carbon nanotube transponder by detectingsaid molecular label.
 52. The method according to claim 48 or 49,further comprising coating the outer surface of said energy-releasingcarbon nanotube transponder with a biocompatible coating selected fromthe group consisting of polylactic acid (PLA), polyglycolic acid (PGA),poly lactide co-glycolide (PLGA) and chitosan.
 53. The method accordingto claim 48 or 49, further comprising recharging each said nanocapacitorwithin said plurality of energy-releasing carbon nanotube transpondersfor allowing multiple treatments.
 54. The method according to claim 48or 49, further comprising guiding said plurality of energy-releasingcarbon nanotube transponders through an electric field.
 55. The methodof guiding an energy-releasing carbon nanotube transponder through anelectric field comprising: (a) determining the optimum placement of atleast one electrical electrode; (b) determining the optimum electricalcharacteristics of the electrical field to be generated from at leastone said electrode and; (c) applying said electrical field to guide themigration of an energy-releasing carbon nanotube transponder.
 56. Themethod according to claim 55, further comprising: (a) binding amolecular label selected from the group consisting of technetium andindium-111 to said energy-releasing carbon nanotube transponder; and (b)tracking said energy-releasing carbon nanotube transponder by detectingsaid molecular label.